Synthetic Oligomers Mimicking Capsular Polysaccharide Diheteroglycan are Potential Vaccine Candidates against Encapsulated Enterococcal Infections

Synthetic Oligomers Mimicking Capsular Polysaccharide Diheteroglycan are Potential Vaccine Candidates against Encapsulated Enterococcal Infections Full article

Journal

ACS Infectious Diseases
ISSN: 2373-8227

Output data

Year: 2020, Volume: 6, Number: 7, Pages: 1816-1826 Pages count : 11 DOI: 10.1021/acsinfecdis.0c00063

Authors

Laverde D ¹ , Romero-Saavedra F ¹ , Argunov D A ² , Enotarpi J ³ , Krylov V B ² , Kalfopoulou E ¹ , Martini C ⁴ , Torelli R ⁵ , Marel G A van der ³ , Sanguinetti M ^5,4 , Codée J D C ³ , Nifantiev N E ² , Huebner J ¹

Affiliations

1	Division of Paediatric Infectious Diseases, Dr. von Hauner Children’s Hospital, Ludwig Maximilians University, Munich 80337, Germany
2	N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119334, Russia
3	Bio-Organic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden 2333 CC, Netherlands
4	Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Rome 00168, Italy
5	Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome 00168, Italy

Infections caused by Enterococcus spp. are a major concern in the clinical setting. In Enterococcus faecalis, the capsular polysaccharide diheteroglycan (DHG), composed of ß-d-galactofuranose-(1 → 3)-ß-d-glucopyranose repeats, has been described as an important virulence factor and as a potential vaccine candidate against encapsulated strains. Synthetic structures emulating immunogenic polysaccharides present many advantages over native polysaccharides for vaccine development. In this work, we described the synthesis of a library of DHG oligomers, differing in length and order of the monosaccharide constituents. Using suitably protected thioglycoside building blocks, oligosaccharides up to 8-mer in length built up from either Galf-Glcp or Glcp-Galf dimers were generated, and we evaluated their immunoreactivity with antibodies raised against DHG. After the screening, we selected two octasaccharides, having either a galactofuranose or glucopyranose terminus, which were conjugated to a carrier protein for the production of polyclonal antibodies. The resulting antibodies were specific toward the synthetic structures and mediated in vitro opsonophagocytic killing of different encapsulated E. feacalis strains. The evaluated oligosaccharides are the first synthetic structures described to elicit antibodies that target encapsulated E. faecalis strains and are, therefore, promising candidates for the development of a well-defined enterococcal glycoconjugate vaccine.

Laverde D. , Romero-Saavedra F. , Argunov D.A. , Enotarpi J. , Krylov V.B. , Kalfopoulou E. , Martini C. , Torelli R. , Marel G.A.v.d. , Sanguinetti M. , Codée J.D.C. , Nifantiev N.E. , Huebner J.
Synthetic Oligomers Mimicking Capsular Polysaccharide Diheteroglycan are Potential Vaccine Candidates against Encapsulated Enterococcal Infections
ACS Infectious Diseases. 2020. V.6. N7. P.1816-1826. DOI: 10.1021/acsinfecdis.0c00063 WOS Scopus OpenAlex

≡ Web of science:	WOS:000595290900031
≡ Scopus:	2-s2.0-85087800233
≡ OpenAlex:	W3022437500